Cancer, a diverse group of diseases characterized by uncontrolled growth of abnormal cells, is a major worldwide problem. It is a fatal disease standing next to the cardiovascular disease. Although the cancer research has led to a number of new and effective solutions. the medicines used as treatments have clear limitations and unfortunately cancer is projected as the primary cause of death in the future. Currently, there is a huge scientific and commercial interest in the discovery of potent, safe and selective anticancer drugs.
Cancer chemotherapy is the treatment that is performed that involves numerous agents such as docetaxel, vinorelbine, mitoxantrone and estramustine. These agents deactivate the cancer cells production. The general disadvantage of chemotherapy, no matter of type of cancer, is the drugs cannot discriminate between fast-growing cells and kills all cells whether they are part of controlled or uncontrolled process. Acting that way, chemotherapy kills and ‘good cells’, including hair follicles, causing typical side effects such as hair loss and other. Thus, the two most important defects of most contemporary anti-cancer agents are that                1. They exhibit poor selectivity toward cancer cells versus normal cells and        2. Poor efficacy against slow-growing tumors.        
So there is need for new potent anticancer compounds that exhibit selectivity for cancerous cells over normal cells. Accordingly, there is still a need in the art for potent cytotoxic agents for use in cancer therapy without having adverse effects on normal cells. Furthermore, there is also great need for additional anticancer agents that are easy to synthesis and are cost effective. Thus, one aim of the present invention is the provision of compounds which are potent anticancer agents that are non-toxic to normal cells and are easy to synthesize.
Natural as well as synthetic coumarins have recently drawn much attention due to its diverse pharmacological activities. Coumarin containing compounds have been demonstrated to have anticancer properties ((1) Kostova, I. Curr. Med. Chem. 2005, 5, 29. (2) Musa, M A.; Cooperwood, J. S. Curr. Med. Chem. 2008, 15, 2664). Recently, Lee et al. reported that Neo-Tanshinlactone, showed significant inhibition against two ER+ human breast cancer cell lines and was 10-fold more potent and 20-fold more selective as compared to Tamoxifen ((3) (a) Yizhou, D.; Quan, S.; Yi, N. L.; Xiang, W.; Kenneth. F. B.; Kuo, H. Lee. J. Med. Chem. 2009, 52, 3586. (b) Xihong, W.; Kyoko, N. G.; Kenneth, F. B.; Ming, J. D.; Yun, L. L.; Tian, S. W.; Kuo, H. Lee, J. Med. Chem. 2006, 49. 5631).
The recognition of key structural features within coumarin family is crucial for the design and development of new analogues with improved activity and for the characterization of their mechanism of action and potential side effects. The different substituent's in the coumarin nucleus strongly influence the biological activity of the resulting derivatives.
In continuation of our interest, in this class of compounds, ((4). (a) Sashidhara, K. V.; Kumar, A.; Kumar, M.; Sonkar, R; Bhatia, G.; Khanna, A. K. Bioorg. Med. Chem. Lett. 2010, 20, 4248. (b) Sashidhara, K. V.; Rosaiah, J. N.; Kumar, A.; Bhatia, G.; Khanna, A. K. Bioorg. Med Chem. Lett. 2010, 20, 3065. (c). Sashidhara, K. V., Kumar, A., Kumar, M., Srivastava, A., Puri, A. Bioorg. Med. Chem. Lett. 2010, 20 6504. (d) Sashidhara, K. V.; Rosaiah, J. N.; Bhatia, G.; Saxena, J. K. Eur. J. Med. Chem. 2008, 43, 2592) We embarked on the synthesis of novel coumarin derivatives as anticancer agents ((5). (a). Sashidhara, K. V., Kumar, A., Kumar, M., Sarkar, J., Sinha, S. Bioorg. Med. Chem. Lett. 2010, 20, 7205. (b) Sashidhara, K. V.; Rosaiah, J. N.; Kumar, M., Gara, R. K., Nayak, L. V., Srivastava, K., Bid, H. K., Konwar, R. Bioorg. Med. Chem. Lett. 2010, 20, 7127). Herein, we wish to describe the synthesis and biological evaluation of novel selective anticancer agents.
In the design of new drugs, the development of hybrid molecules through the combination of different pharmacophores may lead to compounds with interesting biological profiles. In recent years, combination chemotherapy with agents possessing different mechanisms of action is one of the methods that is being adopted to treat cancer. Therefore, a single molecule containing more than one pharmacophore, each with different mode of action could be beneficial for the treatment of cancer ((6). Mayur, Y. C.; Peters, G. J.; Prasad, V. V.; Lemo, C.; Sathish, N. K. Curr. Cancer Drug Targets 2009, 9, 298. (7). Solomon, V. R.; Hu, C.; Lee, H. Bioorg. Med. Chem 2009, 17, 7585). Adopting this approach, several research groups have recently reported hybrid molecules by coupling coumarins with different bioactive molecules.
The preparation and use of coumarin-resveratrol hybrids having the general formula shown in Formula A as antiplatelet agents are reported by (8) Vilar, S.; Quezada, E.; Santana, L.; Uriarte, E.; Yanez, M.; Fraiz, N.; Alcaide, C.; Cano, E.; Orallo, F. Bioorg. Med. Chem. Lett. 2006, 16, 257.

The preparation and use of coumarin-maleimides hybrids having the general formula shown in Formula B as protein and antibody labelling agents are reported by (9) Song, H. Y.; Ngai, M. H.; Song, Z. Y.; MacAry, P. A.; Hobley, J.; Lear, M. J. Org. Biomol. Chem. 2009, 7, 3400.

The preparation and use of coumarin-lipoic acid conjugates having the general formula shown in Formula C as antioxidant and antiinflammatory agents are reported by (10). Melagraki, G.; Afantitis, A.; Igglessi, M. O.; Detsi, A.; Koufaki, M.; Kontogiorgis, C.; Hadjipavlou L. D. Eur. J. Med. Chem. 2009, 44, 3020.

The preparation and use of coumarin-stilbene hybrids having the general formula shown in Formula D as anticancer agents are reported by (11). Belluti, F.; Fontana, G.; Bo, L. D.; Carenini, N.; Giommarelli, C.; Zunino, F. Bioorg. Med. Chem. 2010, 18, 3543.

Furthermore, preparation and use of coumarin-chalcone hybrids having the general formula shown in Formula E as anticancer agents are disclosed by (12). Bombardelli, E.; Valenti, P. WO 01/17984 A1, 2001 and U.S. Pat. No. 6,767,916 B2.

But these compounds are not selective towards the cancer cell lines and also used in combination with other drugs. Keeping in mind these drawbacks, the Applicant has now synthesized highly selective coumarin/chalcone derivatives by a novel method, said derivatives are useful as anticancer agents. The anticancer selectivity of these novel compounds is due to appropriate positioning of the substituent, like the chalcone moiety at 6-position of benzocoumarin ring that enhances the activity and reduces toxicity. The compounds of this invention are a new structural class of coumarin chalcone that differ in significant ways from the previously known compounds. Representative examples of this invention are active as anti-tumor agents in mice bearing human tumor xenografts of cervical and prostrate carcinoma, when dosed either intravenously or orally.